HEMATOLOGICAL RESPONSE OF PATIENTS WITH MYELODYSPLASTIC SYNDROME TO ANTITHYMOCYTE GLOBULIN IS ASSOCIATED WITH A LOSS OF LYMPHOCYTE-MEDIATEDINHIBITION OF CFU-GM AND ALTERATIONS IN T-CELL RECEPTOR V-BETA PROFILES

We have demonstrated that 44% of myelodysplastic syndrome (MDS) patien ts with cytopenia have a haematological response to antithymocyte glob ulin (ATG). Three ATG responders and two non-responders with refractor y anaemia were further studied for lymphocyte-mediated inhibition of b one marrow using a standard CFU-GM assay. In responders, peripheral bl ood lymphocytes (PBL) added at a 5:1 ratio suppressed CFU-GM by 54 +/- 9% (P = 0.04) and was reversed by ATG treatment. Pre-treatment marrow depleted of CD3 lymphocytes, increased CFU-GM by 32% (P = 0.02) in an ATG responder, but not in a nonresponder. CD3 lymphocytes from 6-mont h post-treatment marrow did not inhibit pre-treatment CFU-GM, indicati ng ATG had affected the T cells. Pre-treatment marrow depleted of CD8 lymphocytes, increased CFU-GM by 60% (P = 0.01) and 49% (P = 0.03) in two ATG responders, but not in a non-responder. Inhibition required ce ll-cell interaction through MHC I. TCRV beta families, analysed by SSC P, changed from clonal to polyclonal in one ATG responder after 6 mont hs, but clones persisted in a non-responder. These results indicate pa tients with refractory anaemia who respond to ATG have CDS T-cell clon es that mediate MHC-I-restricted suppression of CFU-GM which are repla ced by polyclonal T cells that do not suppress CFU-GM after ATG treatm ent.